ArticleNature communications2025
Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- Epigenetic Activation of the KDM6B-DKK1 Axis Promotes Colorectal Cancer Peritoneal Metastasis Through Wnt/β-Catenin-Associated EMT.Journal of cellular and molecular medicine · 2026Article
- STRAP promotes hepatocellular carcinoma progression through activation of an STRAP/Wnt-β-catenin/STRAP positive feedback loop.iScience · 2026Article
- Bone-derived Osterix+ osteolineage cells are a source of tumor-promoting myofibroblastic cancer-associated fibroblasts in breast cancer.Nature communications · 2026Article
- DKK1 in Cancer: A Bench-to-Bedside Review of Molecular Mechanisms and Clinical Applications.Cancers · 2026Review
- The Dickkopf-1 (DKK1) Dichotomy in Oncology: New Insights on Tumor Progression and Immune Regulation.International journal of molecular sciences · 2026Review
- The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.International journal of surgery (London, England) · 2026Article
- Cancer-associated fibroblast heterogeneity and its role in reshaping immunotherapy in solid cancers: potential strategies and clinical promise.Frontiers in cell and developmental biology · 2026Review
- Immunomodulation by platelet-derived DKK1: potential for controlling disease and pathology in leishmaniasis and implications for other infectious diseases.Frontiers in immunology · 2026Review
- Cancer-associated fibroblast secreted DKK1 promotes the immunosuppressive tumor microenvironment and colorectal cancer resistance to chemotherapy.Cancer letters · 2025Article
- Cancer-Associated Fibroblasts: Origin, Classification, Tumorigenicity, and Targeting for Cancer Therapy.MedComm · 2025Review
- The Emerging Role of CKAP4 in GI Cancer: From Molecular Pathways to Clinical Applications.Current oncology (Toronto, Ont.) · 2025Review
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone. By using genetic approaches, we find that bone-derived DKK1 contributes to the systemic DKK1 elevation in tumor-bearing female mice, while CAFs contribute to DKK1 at primary tumor site. Systemic and bone-specific DKK1 targeting reduce tumor growth. Intriguingly, deletion of CAF-derived DKK1 also limits breast cancer progression, without affecting its levels in circulation, and regardless of DKK1 expression in the tumor cells. While not directly supporting tumor proliferation, stromal-DKK1 suppresses NK cell activation and cytotoxicity by downregulating AKT/ERK/S6 phosphorylation. Importantly, increased DKK1 levels and reduced cytotoxic NK cells are detected in women with progressive breast cancer. Our findings indicate that DKK1 represents a barrier to anti-tumor immunity through suppression of NK cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.